title: Detection of high levels of Survivin-immunoglobulin M immune complex in sera from hepatitis C virus infected patients with cirrhosis.
abstract: OBJECTIVE
  The identification and surveillance of patients with liver dysfunctions and the discovering of new disease biomarkers are needed in the clinical practice. The aim of this study was to investigate on Survivin-immunoglobulin (Ig)M immune complex (IC) as a potential biomarker of chronic liver diseases.
  
  
  METHODS
  Serum levels of Survivin-IgM were measured using an enzyme-linked immunoassay that had been standardized and validated in our laboratory in 262 individuals, including healthy subjects and patients with chronic viral hepatitis, cirrhosis and hepatocellular carcinoma (HCC).
  
  
  RESULTS
  Survivin-IgM IC was lower in healthy subjects (median, 99.39 AU/mL) than in patients with chronic viral hepatitis (median, 148.03 AU/mL; P = 0.002) or with cirrhosis (median, 371.00 AU/mL; P < 0.001). Among patients with cirrhosis, those with hepatitis C virus (HCV) infection showed the highest level of Survivin-IgM IC (median, 633.71 AU/mL; P < 0.001). The receiver-operator curve analysis revealed that Survivin-IgM accurately distinguishes HCV correlated cirrhosis from chronic viral hepatitis (area under the curve [AUC], 0.738; sensitivity, 74.5%; specificity, 70.7%). A multivariate logistic regression model, including Survivin-IgM IC, aspartate aminotransferase (AST) and AST/alanine aminotransferase (ALT) ratio increased the prediction accuracy for the identification of the cirrhotic HCV patients (AUC, 0.818; sensitivity, 87.2%; specificity, 65.9%). Conversely, Survivin-IgM IC significantly decreased in HCC patients (median, 165.72 AU/mL; P = 0.022).
  
  
  CONCLUSIONS
  Our results suggest that Survivin-IgM immune complex may be used as a potential biomarker for liver damage, particularly for the identification of the HCV-related cirrhotic population.
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy; Institute of Translational Pharmacology, CNR, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Matteucci
authors.forename: Roberta
authors.initials: R
authors.lastname: Sorrentino
authors.forename: Lia
authors.initials: L
authors.lastname: Bellis
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Ettorre
authors.forename: Valentina
authors.initials: V
authors.lastname: Svicher
authors.forename: Roberto
authors.initials: R
authors.lastname: Santoro
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vennarecci
authors.forename: Alessandra
authors.initials: A
authors.lastname: Biasiolo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pontisso
authors.forename: Daria
authors.initials: D
authors.lastname: Scacciatelli
authors.forename: Luca
authors.initials: L
authors.lastname: Beneduce
authors.forename: Cesare
authors.initials: C
authors.lastname: Sarrecchia
authors.forename: Paolo
authors.initials: P
authors.lastname: Casalino
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pierimarchi
authors.forename: Enrico
authors.initials: E
authors.lastname: Garaci
authors.forename: Claudio
authors.initials: C
authors.lastname: Puoti
authors.forename: Guido
authors.initials: G
authors.lastname: Rasi
keywords: Survivin; disease biomarkers; hepatitis C; hepatocellular carcinoma; immune complexes; liver cirrhosis